Edible, baked compositions containing cholestyramine

ABSTRACT

The edible baked composition delivers cholestyramine in a palatable, pleasant tasting form. Embodiments include a nutrition bar and a cookie. The composition is useful for the control of endogenous cholesterol levels in humans.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 206,197, filed June 13, 1988, now U.S. Pat. No. 4,931,280.

BACKGROUND OF THE INVENTION

The present invention relates to an edible, baked composition which willhelp control endogenous terol levels when ingested. More specifically,the composition contains cholestyramine which is useful in the controlof cholesterol or lipid levels of the blood.

Hypercholesteremia, which is also known as high blood cholesterol level,is believed to be responsible in many cases for atherosclerosis.Therefore, it is exceedingly desirable to effect a reduction of theblood cholesterol level in adult, atherosclerotic patients. This hasbeen done heretofore primarily through the use of low fat diets andmedications. However, in many patients this is not sufficient tomaintain the cholesterol within the desired limits. Accordingly, it isdesirable to administer to the patient a cholesterol lowering agent.

Cholesterol and/or lipid reducing agents are useful in the treatment ofarterial plaque formation (i.e. atherosclerosis). These medicinalagents, however, must be administered on a regular, periodic basis inorder to exhibit their beneficial effects Moreover, when formulated astablet, capsule or liquid dosages, these medicaments have the appearanceand character of medicines used in the treatment of sickness anddisease. Consequently, patients for whom cholesterol or lipid reducingagents have been prescribed will have an aversion toward routine, dailyingestion of such medicaments.

In particular, cholestyramine is a medicament of choice for the controlof cholesterol or lipid levels in humans. Its administration, however,has proved to be problematic from a pharmaceutical compounding point ofview. Not only does the cholestyramine exhibit an unpleasant taste andgritty oral consistency, but it is difficult to ingest and/or swallowunder most conditions and methods employed to form maskingpharmaceutical formulations.

Several attempts have been reported in the literature which attempt tocircumvent these difficulties. For example, in EP86-300236, aningestible anhydrous aggregate comprising starch, a non-cellulosicpolysaccharide and cholestyramine is described. This aggregate is acandy which by reason of its extreme sweetness masks the unpleasanttaste of the medicament involved. Another example, U.S. Pat. No.3,974,272, also discloses an oral formulation containing cholestyramine.In this instance, the formulation has a base of milk or fruit juice andcontains a hydrophilic colloid which masks the cholestyramine until ithas passed the taste receptors along the human alimentary canal.

The sweetness and refined character of such candy confections containingmedicaments like cholestyramine are not desirable for an ediblemedicament composition. The refined ingredients present do not deliverappropriate bulking character to the gut. These disadvantages detract ormay, in certain instances, negate the advantage provided by the controlof cholesterol level in the blood by cholestyramine.

It would be advantageous to develop a food product for administration ofcholestyramine which also contains non-nutritive bulking agents. Itwould seem that such a food product could be adapted from so-calledbaked compositions. These baked compositions, however, require the useof high temperatures for congealing and solidifying their ingredients.The high temperature necessary for the baking in such instances willcause decomposition and degradation of cholestyramine. As a result,baked compositions of such ingredients as flour and solid sugars navenot been useful as vehicles for the oral administration of cholesteroland lipid control agents such as cholestyramine.

It is an object of the invention, therefore, to develop a bakedcomposition containing cholestyramine which can be prepared attemperatures low enough to avoid or substantially eliminate thedegradation and decomposition of cholestyramine. It is another object ofthe invention to develop a baked composition which is pleasant tasting,has a desirable oral constituency and which masks the unpleasant tasteof cholestyramine. It is a further object of the invention to develop abaked composition which will deliver cholestyramine in a form that willenable efficient finding of bile salts and other cholesterol and lipidcomponents present in the gut. Yet another object of the invention is todevelop a medicinal formulation which will deliver a level ofcholestyramine that will control cholesterol and lipid levels in humans.

SUMMARY OF THE INVENTION

These and other objects are achieved by the present invention which isdirected to an edible, baked composition which is composed of a bakedmatrix of an edible oil, mono, oligo and polysaccharides, water,flavoring and cholestyramine which is present in an amount of about 5 toabout 20% by weight relative to that of the composition.

The mono, oligo and polysaccharides present in the baked matrix includeamong others, an acid hydrolyzed starch binder which functions to form acongealed mass of the ingredients present in the baked matrix Inspecific part, the matrix ingredients are baked at a maximum temperatureof about 150° C. to about 180° C. for no longer than about 20 minutesYet they produce a firm baked composition because of the presence of thestarch binder. Moreover, the cholestyramine present inside the bakedmatrix is substantially prevented from decomposing or degrading.

Under the preferred weight proportions of the oil, mono, oligo andpolysaccharides, starch binder and cholestyramine present in the bakedmatrix, the cholestryamine and starch binder form a crisp, crunchyexterior and a sot chewy interior for the baked matrix.

Preferred embodiments include a baked matrix which contains a sweeteningagent, a baked matrix which is formed from flour and optional leaveningand non-cholesterol containing synthetic egg ingredients; a baked matrixhaving the form, texture and constituents characteristic of acookie-like product; a baked matrix having the ingredients andcharacteristics of a nutritional bar-like composition; a baked matrixformed from all-natural ingredients; and a baked matrix containing oatbran which also controls endogenous cholesterol levels.

DETAILED DESCRIPTION OF THE INVENTION

The edible, medicinal composition of the present invention deliversreasonable levels of cholestyramine in the gut and will controlcholesterol and lipid levels in humans when it is ingested on a regularbasis. The medicinal composition is a pleasant tasting, orallyingestible substance which has additional nutritional and vitamin value.Its cookie-like or nutritional bar-like qualities make it a desirablemeans for administration of an otherwise unpleasant tasting medicament.

The baked matrix forming the medicinal composition of the inventioncontains a high proportion f cholestyramine as well as a starch binder.The starch binder, cholestyramine and other ingredients, such as theedible oil, combine during the baking process to readily undergo acrisping and congealing transformation similar to the Browning orMaillard reaction. The two ingredients, cholestyramine and starchbinder, are believed to facilitate this low temperature baking so thatthe internal temperatures of the composition do not reach degradation ordecomposition levels of cholestyramine during baking.

The saccharides of low to high molecular weights used as ingredients inthe baked matrix include a starch binder, a starch, acid hydrolyzedstarch, dextrins from high to moderate molecular weight, partiallyhydrolyzed dextrins of low to moderate molecular weight, simple andcomplex sugars such as glucose, lactose, fructose, raffinose, galactose,sucrose, invert sugar, honey, molasses, and other similar saccharidesoligomers and polymers. In addition, artificial sweeteners such assaccharine, aspartame and other dipeptide sweeteners may be present.

The oligo and polysaccharides include amylose, amylopectin,polydextrins, oligodextrins of from 6 to 14 monomeric units in length,enzyme modified polydextrin, enzyme modified forms of the foregoingpolysaccharides and acid and base hydrolyzed forms of the foregoingoligo and polysaccharides. Additional sugars useful as mono and oligosaccharides according to the invention include sorbose, allose, manose,iodose, talose, maltose and the like.

The edible oil employed as an ingredient in the baked matrix may be asaturated or unsaturated liquid fatty acid, its glyceride derivatives orfatty acid derivatives of plant or animal origin or a mixture thereof.Oils from natural sources that contain cholesterol and oils that thebody will convert to cholesterol, however, are to be avoided. Palm oil,soybean oil, corn oil, saffron oil, sunflower seed oil, palmitic oil,linoleic oil, and hydrocarbon acid oils having chain lengths from C-10to C-30 can be used as the oil ingredient of the baked matrix. Usually,a fatty glyceride compound derived from vegetable or marine oils or asynthetic produced congener thereof will comprise the edible oil used.Additional examples include lauroyl, myristoyl, stearoyl, oleoyl,behenoyl, arachidonoyl, erucoyl oils and the like. In addition to beingobtained from the foregoing plant sources, these fats and oils may alsobe obtained from cotton seed, rape seed, peanut, olive, sesame, rice,wallflower, nasternum, mustard and other similar seed sources. Marinesources include whale, sardine, herring, menhaden and pilchard oils.Also included are di and triglycerides of the fatty glyceride compoundsused as oils in the invention which can be the foregoing medium to longchain organic acids in combination with short chain organic acids suchas acidic, propionic, butyric, valeric and caproic acids. Mixtures ofthe foregoing oils can also be used as the oil component according tothe invention.

Additional ingredients present in the baked matrix according to theinvention may be selected from cereals, rolled grains, nutmeats, peanutbutter, cocoa, raisins, chocolate chips (e.g. those not including milkor dairy products), butterscotch chips, nutmeats including whole andchopped meats from edible nuts including walnuts, hickory nuts, hazelnuts, brazil nuts, peanuts, macadamia nuts, pecans, cashews, almonds andthe like. Additionally, such nutmeat ingredients as fruits, dried fruitsand cellulosic fibers, bran, ground bran, grain hulls, ground corn cobsand powdered bark can be used as additional ingredients in thecomposition. It is especially preferred that the composition contain oatbran. This bran can by itself control the sorption and resorption ofcholsterol containing materials in the gut. Its combination withcholestyramine enhances this control effect of either the oat bran orthe cholestyramine. Preservatives such as BHA, BHT and potassium sorbatemay also be present. These ingredients provide nutrition, vitamins,bulking, ruffage and other similar desirable nutritious properties forthe baked matrix according to the invention.

A preferred embodiment according to the invention is a cookie-like bakedmatrix. This embodiment can be formulated from flour, water, an optionalleavening agent, acid hydrolyzed starch binder and edible oil,flavoring, and optional sweetening agent, and oligo and polysaccharides.The flour employed may be selected from wheat, oat, rice, soybean, corn,and other similar grain flours. The sweetening oligosaccharides mayinclude honey, molasses, sucrose, invert sugar, fructose or mixturesthereof. The edible oil may include soybean oil, palm oil andtriglycerides.

Another preferred embodiment is a nutritional bar-like compositionformed as a baked matrix according to the invention. As in the cookie,this nutritional bar will contain such ingredients as the acidhydrolyzed starch binder, cholestyramine, edible oil and mono, oligo andpolysaccharides. However, it will also include rolled grains, a loweramount of edible oil and, no flour, but rather solid mono andoligosaccharides such as sucrose, lactose, manose, maltose and dextrinsand partially hydrolyzed dextrins.

It is preferred to have in both the cookie and bar portions of ruffageand bulking ingredients such as non-digestible cellulose, bran and thelike. The presence of such ingredients helps lower cholesterolresorption in the gut and promotes bowel regularity.

Both the cookie and the nutritional bar can have crispy exteriors anddoughy or chewy interiors. The texture of the cookie will be smoothwhile the texture of the nutritional bar will be composed of largeparticulate matter, some of which is non-nutritive and is bulkproducing.

The weight ratios of ingredients present in the baked matrix medicinalcomposition according to the invention will in part determine the crispyexterior and the chewy interior of the composition. Moreover, the weightratios of ingredients permit the congealment, gellation andtransformation at a lower temperature relative to those bakingtemperatures typically used to produce baked products in this field. Ingeneral, it has been found that the weight ratio of edible oil tocholestyramine is from about 1:1 to about 1:4. The weight ratio of mono,oligo and polysaccharides to cholestyramine is from about 10:1 to about2:1. In similar fashion, the weight ratio of acid hydrolyzed starchbinder will be from 5 to 1 to about 1 to 1 relative to the weight ofcholestyramine present. In general, the sum of the weights of the acidhydrolyzed starch binder and cholestyramine will be from about 10% toabout 50 weight percent of the total composition. The weight ratio ofedible oil to mono, oligo and polysaccharides will be from about 1:10 toabout 1:2. In general, the acid hydrolyzed starch binder will comprisepart of the mono, oligo an polysaccharides; however it may also bepresent alone or as a separate ingredient.

According to the invention, an especially preferred composition is abaked matrix nutrition bar composed of about 5 to 20 weight percentedible fiber, about 5 to 15 weight percent edible plant oil, about 5 to25 weight percent polysaccharides selected from starch, dextrin,amylopectin, amylose, hydrolyzed or enzymatically treated forms thereofand mixtures thereof, about 20 to 30 weight percent acid hydrolyzedstarch binder, about 10 to 25 weight percent mono or oligosaccharidesselected from glucose, fructose, sucrose, invert sugar, lactose,maltose, galactose, hydrolyzed dextrins and mixtures thereof, about 5 to20 weight percent rolled whole grains, about 5 to 15 percent water,about 5 to 20 percent cholestyramine, about 1 to 2 percent flavoring andspice and the remaining percentage of fruits, nuts, optional proteinpowder, vitamins and minerals. This composition has a pleasant taste andmasks the off-taste of the cholestyramine. Moreover, in this nutritionbar, the exterior surfaces are crispy when the product has been baked ata temperature of about 150° C. for about 5 to 8 minutes. The interior isof a chewy texture.

Generally, this nutrition bar composition according to the inventionwill deliver to the gut an amount of cholestyramine sufficient for theefficient control of lipid and cholesterol level in the bloodstream whenfrom 2 to 5 nutrition bars per day are consumed at regular intervals. Inaddition, the nutrition bar will deliver complex carbohydrates, protein,vitamins, minerals and other nutrients necessary or beneficial for dailyactivity. The level of cholestyramine present in the gut will be fromabout 3.5g to about 4.5g and will remain substantially constant duringthe periodic ingestion of the nutrition bar. It binds lipid, cholesteroland bile salt containing materials in the gut and permits theirpass-through without sorption or resorption.

Another especially preferred composition according to the invention is abaked matrix cookie having a smooth cookie-like texture. This bakedmatrix cookie is composed of from about 5 to 15 weight percent edibleplant oil, about 5 to 25 percent grain flour such as wheat, oat, rye orrice flour, about 20 to 30 weight percent acid hydrolyzed starch binder,about 5 to 20 weight percent sweetner selected from honey, molasses,sucrose, fructose, invert sugar or a mixture thereof, about 5 to 20weight percent rolled whole grains, about 5 to 20 weight percentcholestyramine, about 2 to 15 weight percent water, flavoring, spice,optional protein powder, vitamins, minerals and other flavoringingredients such as chocolate, butterscotch chips and nuts.

This cookie composition also delivers a desired level of cholestyramineto the gut when from approximately 2 to about 6 cookies per day areconsumed at periodic intervals. In addition to the delivery of desiredlevels of cholestyramine, this preferred cookie composition deliverscomplex carbohydrates, vitamins, minerals and other nutrients necessaryor beneficial for daily activity. Lipids, cholesterol and bile salts arethereby bound in the gut and their pass-through without sorption orresorption is permitted.

When the baked matrix according to the invention is to be prepared, thedry ingredients are blended together in a low speed mixing apparatus.These ingredients include the rolled grains, nuts, fruits, the solidmono, oligo and polysaccharides, and other dry ingredients. After thedry ingredients are thoroughly mixed, the fluid or viscous ingredientsare combined. These include such ingredients as the edible oil,flavoring, spices, and mono and oligo saccharides such as honey,fructose, invert sugar and water. The combined ingredients are mixed ina low speed mixing apparatus for a period of time sufficient to producea substantially homogeneous mixture. The acid hydrolyzed starch binderis combined with the mixture of dry and fluid or viscous ingredientsafter they have been combined into a substantial homogeneouscombination.

Alternatively, the dry ingredients and the fluid or viscous ingredientscan be combined separately. In this instance, the acid hydrolyzed starchbinder will be added to the fluid, viscous mixed ingredients and stirreduntil a substantially homogeneous combination is produced. Then, the twomixtures are combined and mixed.

Following the thorough mixing of the foregoing ingredients, theappropriate selected amount of cholestyramine is added and the entirecombination mixed at low speed for a time sufficient to produce asubstantial homogeneous composition. The sticky, viscous compositionthen extruded as dollops by a wire cutter or other similar extrudingapparatus onto a continuous or batch process baking sheets and placedinto a baking oven for a time sufficient to cause the crisping reactionto occur on the exterior surfaces and to produce a chewy textureinternally. The oven temperature employed will be from about 80˜ toabout 180˜, preferrably about 120˜ to about 160˜ C and most preferrablyabout 150˜ C. The time for baking will approximately be from about 10 toabout 20 minutes. Preferrably about 14 to 18 minutes in time. It hasbeen found that under these conditions the internal temperature of thebaked matrix according to the invention does not reach a high enoughtemperature to cause decomposition or degradation of the cholestyraminepresent.

The invention will be further illustrated by the following examples.These examples, however, are not meant to limit the scope of the claimsor the description of the invention presented in the foregoingspecification.

EXAMPLE 1 Cholestyramine Nutritional Bar

The following dry ingredients were combined in a mixing bowl and mixedfor approximately 3 minutes at low speed to produce a substantiallyhomogeneous blend of dry ingredients. In a separate mixing bowl, thefluid and semi-viscous ingredients were combined and mixed at low speedto produce a substantially homogenous fluid mixture. The acid hydrolyzedstarch binder having the tradename "Starch-Tender G" was combined withthe fluid mixture and then further mixed on low speed for approximately3 minutes until a substantially homogeneous combination was produced.The syrup mixture was added to the dry mixture while blending at lowspeed for approximately 5 minutes or until a substantially homogenouscomposition was produced. The sticky, semi-rigid dough was then extrudedon a wire-cut machine into bar-like configurations and was baked forapproximately 16 minutes at a temperature of about 145° C. to produce acrispy texture, a chewy interior nutritional bar.

The following list of ingredients and proportions were employed in theforegoing procedure to produce the nutritional bar described in thisexample.

    ______________________________________                                        Ingredients        Weight % of Formulation                                    ______________________________________                                        Rolled Oats        3.6 Weight %                                               Oat Bran           3.3 Weight %                                               Currant Raisins    1.4 Weight %                                               Almonds            1.4 Weight %                                               Soy Polysaccharides                                                                              1.4 Weight %                                               Honey              8.8 Weight %                                               Fructose           55 Weight %                                                (Invert Sugar Composition)                                                                       23.5 Weight %                                              Sugar (Sucrose)    21.9 Weight %                                              Soybean Oil        6.8 Weight %                                               Water              8.5 Weight %                                               Cinnamon           1 Weight %                                                 Starch - Tender Gel G                                                                            4 Weight %                                                 Cholestyramine     14.8 Weight %                                              Vanilla            0.8%                                                       ______________________________________                                    

EXAMPLE 2 Composition and Procedure for Baked Cholestyramine CookieContaining Flour

    ______________________________________                                                     Per-                    Per-                                                  cent                    cent                                     Ingredient   W/W     Ingredient      W/W                                      ______________________________________                                        Water        30.7    Unbleached Wheat                                                                              19.6                                     White Sugar Sucrose                                                                        5.5     Flour                                                    Brown Sugar Sucrose                                                                        6.7     Baking Soda     0.3                                      Soy Bean Oil 9.2     Salt            0.1                                      Molasses     0.5     Dates           5.7                                      Natural Brown Sugar                                                                        0.1     Oates           3.5                                      Flavor               Medium Coconut Oil                                                                            2.9                                      Cinnamon     0.1     Sesame Seed     2.0                                      Narural Vanilla                                                                            0.1     Cholestyramine  13.0                                                                          100.0%                                   ______________________________________                                    

The water, sugars, soy bean oil, molasses, vanilla, cinnamon and coconutoil for 5 minutes are mixed together and then the flour, baking soda andsalt may be blended-in and mixed about 4 minutes. The dates, oats,sesame seeds and cholestyramine may be thereafter added and mixed about3 minutes. The dough is measured into dollops to provide round cookiesabout 2 inches in diameter The dollops may be baked for about 14 minutesat about 300° F (about 150° C.) to provide the finished cookie.

EXAMPLE 3 Taste Testing

The Nutritional Bars described in Example 1 were manufactured on a largescale batch processing line and packaged in foil pouches under nitrogenThe foil pouched Bars were stored at room temperature, 45° C., 37° C.and 75% relative humidity and refrigerated at 4° C. To determine theirpalatability and storage properties, these Bars were periodicallytaste-tested and checked for physical characteristics such asconsistency, color, texture and mouth-feel by a four member taste panel.Samplings were made by the panel after one month and three months at 37°C. and 75% relative humidity, two months at 45° C, three months and sixmonths at room temperature and six months refrigerated at 4° C. Thepanel determined that the taste and the physical characteristics of theBars were acceptable at all sampling times under the conditions stated.

I claim:
 1. An edible, baked composition in the form of a cookiesuitable for medicinal use comprising:a baked matrix comprised of water,an edible oil, mono, oligo or polysaccharides, flavoring, andcholestyramine which is present in an amount of about 5 to 20 percent byweight relative to the weight of said composition, said compositionbeing baked for a time period and at a temperature effective forproviding a therapeutically effective dosage of undecomposedcholestyramine in said baked composition.
 2. An edible, bakedcomposition in the form of a nutritional bar comprising:a baked matrixcomprised of water, an edible oil, mono, oligo or polysaccharides,flavoring, and cholestyramine which is present in an amount of about 5to 20 percent by weight relative to the weight of said composition, saidcomposition being baked for a time period and at a temperature effectivefor providing a therapeutically effective dosage of undecomposedcholestyramine in said baked composition.
 3. A edible composition ofclaim 1 or 2 wherein the composition has a crispy exterior and a chewyinterior.